The drug methaqualone is an effective sedative/hypontic which has anti-convulsant, as well as minor analgesic and antitussive properties. When first introduced it was promoted as a non- barbiturate sedative/hypontic having little or no habituating potential. In spite of this early optimism, methaqualone has become a common "recreational" or "abuse" drug which has resulted in numerous deaths from overdose. The biochemical basis for its various pharamcological functions and high abuse potential remain largely unexplored. The overall objective of this proposal is to study the various pharmacological properties of MQ through an investigation of the receptor system(s) which specifically and functionally bind methaqualone. These objectives will be accomplished through: 1) the synthesis of tritiated methaqualone and its use for the development of a MQ specific radioreceptor assay, which in turn will be used for the determination of which various classes of drugs inhibit specific MQ binding in brain homogenates; 2) the methaqualone receptor systems will be further characterized through a study of the ability of brain homogenates to bind tritiated methaqualone analogues having function specific pharmacological activities and; 3) autoradiographic studies using both tritiated methaqualone and various tritiated methaqualone analogues in order to study whole animal and regional brain binding distribution patterns. The work described in this proposal is expected to significantly advanced our knowledge of all aspects of the pharmacological actions of methaqualone, including its anti-convulsant, analgesic, antitussive and sedative/hypnotic properties.